title: Regulation of colonic epithelial cell turnover by IDO contributes to the innate susceptibility of SCID mice to Trichuris muris infection.
abstract: Tryptophan catabolism via the kynurenine pathway is dependent on the enzyme Indoleamine 2,3-dioxygenase (IDO). Expression of IDO is upregulated in a number of inflammatory settings such as wounding and infection, and the resulting local tryptophan depletion may inhibit the replication of intracellular pathogens. Indo gene expression is upregulated in the gut during chronic infection with the mouse whipworm Trichuris muris. We demonstrate an increase in the rate of colonic epithelial cell turnover after inhibition of IDO in T. muris-infected SCID mice, leading to a significant expulsion of parasite burden. We identify the goblet cell as a novel source of IDO and present data revealing a new role for IDO in the regulation of epithelial cell turnover post-infectious challenge.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, UK. louise.bell@manchester.ac.uk
authors.forename: L V
authors.initials: LV
authors.lastname: Bell
authors.forename: K J
authors.initials: KJ
authors.lastname: Else
mesh_terms: D000818:Animals; D003106:Colon / Q000469:parasitology / Q000473:pathology*; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000201:enzymology* / Q000378:metabolism; D020397:Goblet Cells / Q000201:enzymology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D009687:Nuclear Proteins; D012376:Rodent Diseases / Q000469:parasitology / Q000473:pathology*; D014257:Trichuriasis / Q000469:parasitology / Q000473:pathology / Q000662:veterinary*; D014258:Trichuris / Q000472:pathogenicity*
chemical_list: D004268:DNA-Binding Proteins; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D009687:Nuclear Proteins; D051747:DNA-Activated Protein Kinase; C497264:Prkdc protein, mouse